Leukotrienes are biological compounds formed from arachidonic acid in the leukotriene synthesis pathway. Leukotrienes are synthesized primarily by eosinophils, neutrophils, mast cells, basophils, dendritic cells, macrophages and monocytes. Leukotrienes have been implicated in biological actions including, by way of example only, smooth muscle contraction, leukocyte activation, cytokine secretion, mucous secretion, and vascular function.
FLAP is a member of the MAPEG (membrane associated proteins involved in eicosanoid and glutathione metabolism) family of proteins. FLAP is responsible for binding arachidonic acid and transferring it to 5-lipoxygenase. 5-Lipoxygenase can then catalyze the two-step oxygenation and dehydration of arachidonic acid, converting it into the intermediate compound 5-HPETE (5-hydroperoxyeicosatetraenoic acid), and in the presence of FLAP convert the 5-HPETE to Leukotriene A4 (LTA4).
LTA4 is acted on by LTC4 synthase, which conjugates LTA4 with reduced glutathione (GSH) to form the intracellular product leukotriene C4 (LTC4). LTC4 is transformed to leukotriene D4 (LTD4) and leukotrine E4 (LTE4) by the action of gamma-glutamyl-transpeptidase and dipeptidases. LTC4 synthase plays a pivotal role as the only committed enzyme in the formation of cysteinyl leukotrienes.